Search Results (67)

Theileriosis is considered an economically important disease that may decrease productivity and cause a high mortality rate in livestock. Only a few studies have reported Theileria spp., such as T. sergenti and T. buffeli, in recent decades in Taiwan. In the present study, 401 ticks have been collected on Orchid Island in June 2022 and April 2023. Our environmental investigation for SFTSV unintentionally discovered T. luwenshuni in Haemaphysalis mageshimaensis on Orchid Island via PCR. The PCR products were sequenced, and the detected 18S rRNA gene sequences shared a 99.65–99.93% identity with T. luwenshuni sequences from ticks and ruminants in Myanmar and China. Despite the difficulty in clarifying the source of T. luwenshuni within neighboring regions, our findings provide an updated distribution of T. luwenshuni in Asia. This is not only the first time that T. luwenshuni was found in H. mageshimaensis but also the first report of T. luwenshuni on Orchid Island, Taiwan. Our study indicates that ruminants may be at risk of infection. Therefore, further investigations are needed to determine the distribution of T. luwenshuni among ruminants on Orchid Island and in Taiwan. Full article

Arboviruses pose significant public health challenges globally, particularly in Pakistan, where deforestation, climate change, urbanization, inadequate sanitation, and natural disasters have all contributed to the spread of mosquito-borne flavivirus diseases like dengue fever. The lack of a thorough national surveillance system has made it difficult to determine the extent and distribution of these diseases. Concern has been raised by recent outbreaks of West Nile virus (WNV) and chikungunya (CHIKV) epidemics, which may lead to Zika virus (ZIKV) outbreaks in the future. Additionally, hospital-based surveillance has detected the Japanese encephalitis virus (JEV) in the region. Evidence also points to the presence of additional arboviruses in healthy populations, such as the Karshi virus (KSV), Tamdy virus (TAMV), Crimean–Congo hemorrhagic fever virus (CCHFV), and severe fever with thrombocytopenia syndrome virus (SFTSV). This review aims to address the risk factors linked to these diseases, provide specific policy recommendations for efficient disease prevention and control, and describe the epidemiological trends of these diseases in Pakistan while emphasizing the critical need for improved surveillance and thorough epidemiological investigations. Full article

The prevalence of SFTS is becoming increasingly widespread and is expected to become a significant security issue. The article discusses the prevalence regions and genetic differences in two SFTSV lineages, so as to provide a scientific data basis for the clinical control and prevention of fever with thrombocytopenia syndrome. The literature involving SFTSV patients from 2009 to 2023 and SFTSV complete genome sequences uploaded by NCBI were collected and sorted out, based on time and SFTSV lineage division, we analyzed viral gene sequence. SFTSV patient data were continuously reported from 2009 to 2023, involving five countries including China, South Korea, Japan, Thailand, and Vietnam. There are obvious lineage and host divisions between the SFTSV lineages prevalent in China and abroad. The sources of B-lineage SFTSV samples are mainly concentrated in South Korea, Japan, and the middle and lower reaches of Hubei or Zhejiang in China, with half of the samples coming from humans and half from animals, and the F series SFTSV samples were mainly collected from provinces such as Anhui and Henan in China, with the main source being human patients. The F-lineage SFTSV is the highest proportion in the middle and upper provinces in China. The B lineage has recently appeared in Zhejiang and Taiwan and is prevalent abroad. Using prediction software based on molecular structure prediction technology, analyze the differences between the B and F lineages of SFTSV through prediction methods such as nucleotide mutations, gene recombination, mutation sites, and evolution rates. Conclusively, the differences in SFTSV between B and F lineages may be related to gene recombination of M and L fragments, it was also found that the B lineage had a lower recombination rate and mutation rate than the F lineage, and the evolutionary rate was prominently different. Comparative analysis of the differences in two SFTSV lineage genes could further understand the epidemic status of SFTSV and provide help and more insights for the prevention of the spread of specific types of SFTSV. Full article

H. longicornis is used as an experimental animal model for the study of three-host ticks due to its special life cycle and easy maintenance in the laboratory and in its reproduction. The life cycle of H. longicornis goes through a tightly regulated life cycle to adapt to the changing host and environment, and these stages of transition are also accompanied by proteome changes in the body. Here, we used the isobaric tags for a relative and absolute quantification (iTRAQ) technique to systematically describe and analyze the dynamic expression of the protein and the molecular basis of the proteome of H. longicornis in seven differential developmental stages (eggs, unfed larvae, engorged larvae, unfed nymphs, engorged nymphs unfed adults, and engorged adults). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the differentially expressed proteins (DEPs) were used. In our study, A total of 2044 proteins were identified, and their expression profiles were classified at different developmental stages. In addition, it was found that tissue and organ development-related proteins and metabolism-related proteins were involved in different physiological processes throughout the life cycle through the GO and KEGG analysis of DEPs. More importantly, we found that the up-regulated proteins of engorged adult ticks were mainly related to yolk absorption, degradation, and ovarian development-related proteins. The abundance of the cuticle proteins in the unfed stages was significantly higher compared with those of the engorged ticks in the previous stages. We believe that our study has made a significant contribution to the research on H. longicornis, which is an important vector of SFTSV. In this study, we identified changes in the proteome throughout the H. longicornis development, and functional analysis highlighted the important roles of many key proteins in developmental events (ovarian development, the molting process, the development of midgut, the development and degeneration of salivary glands, etc.). The revelation of this data will provide a reference proteome for future research on tick functional proteins and candidate targets for elucidating H. longicornis development and developing new tick control strategies. Full article

No effective vaccines or treatments are currently available for severe fever with thrombocytopenia syndrome (SFTS), a fatal tick-borne infectious disease caused by the SFTS virus (SFTSV). This study evaluated the potential of ¹¹¹In-labeled anti-SFTSV antibodies targeting SFTSV structural proteins as single-photon emission computed tomography (SPECT) imaging agents for the selective visualization of SFTSV-infected sites. This study used nuclear medicine imaging to elucidate the pathology of SFTS and assess its therapeutic efficacy. Immunostaining experiments confirmed that the anti-SFTSV antibody (N-mAb), which targets the N protein, specifically accumulated in SFTSV-infected Vero E6 cells. ¹¹¹In-labeled N-mAb was successfully prepared using a diethylenetriaminepentaacetic acid (DTPA) chelator, resulting in [¹¹¹In]In-DTPA-N-mAb with high radiochemical purity exceeding 95% and a radiochemical yield of 55%. Cell-binding assays using SFTSV-infected Vero E6 cells demonstrated that [¹¹¹In]In-DTPA-N-mAb binding was detectable even without membrane permeabilization, with the binding intensity correlating with infection levels. In vivo studies using SFTSV-infected A129 mice showed high spleen accumulation of [¹¹¹In]In-DTPA-N-mAb (87.5% ID/g), consistent with SFTSV tropism, compared to 12.3% ID/g in mock-infected mice. SPECT/CT imaging clearly revealed high radioactivity in these regions. Although nonspecific accumulation was noted in the liver and spleen, this issue may be mitigated through antibody modifications such as fragmentation or PEGylation. Overall, [¹¹¹In]In-DTPA-N-mAb is a promising imaging agent for non-invasive visualization of SFTSV-infected sites and may aid in elucidating SFTS pathology and assessing therapeutic efficacy. Full article

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar^−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar^−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar^−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile. Full article

Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness caused by the SFTS virus (SFTSV). We conducted this study to propose a scientific evidence-based treatment that can improve prognosis through changes in viral load and inflammatory cytokines according to the specific treatment of SFTS patients. This prospective and observational study was conducted at 14 tertiary referral hospitals, which are located in SFTS endemic areas in Korea, from 1 May 2018 to 31 October 2020. Patients of any age were eligible for inclusion if they were polymerase chain reaction positive against SFTSV, or showed a four-fold or higher increase in IgG antibody titers between two serum samples collected during the acute and convalescent phases. On the other hand, patients with other tick-borne infections were excluded. In total, 79 patients were included in the study. The viral load of the group treated with steroids was 3.39, 3.21, and 1.36 log₁₀ RNA copies/reaction at each week since the onset of symptoms, and the viral load in patients treated with plasma exchange was 4.47, 2.60, and 2.00 log₁₀ RNA copies/reaction at each week after symptom onset. The inflammatory cytokines were not reduced effectively by any specific treatment except IVIG for the entire treatment period. Secondary infections according to pathogens revealed four bacterial (26.7%) and one fungal (6.7%) infection in the steroid group. The viral load of SFTSV and inflammatory cytokines cannot be decreased by steroid and plasma exchange treatments. Secondary bacterial infections can occur when steroids are administered for the treatment of SFTS. Therefore, caution should be exercised when choosing treatment strategies for SFTS. Full article

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection. Full article

In our prior investigations, we elucidated the role of the tryptophan-to-tyrosine substitution at the 61st position in the nonstructural protein NSsW61Y in diminishing the interaction between nonstructural proteins (NSs) and nucleoprotein (NP), impeding viral replication. In this study, we focused on the involvement of NSs in replication via the modulation of autophagosomes. Initially, we examined the impact of NP expression levels, a marker for replication, upon the infection of HeLa cells with severe fever thrombocytopenia syndrome virus (SFTSV), with or without the inhibition of NP binding. Western blot analysis revealed a reduction in NP levels in NSsW61Y-expressing conditions. Furthermore, the expression levels of the canonical autophagosome markers p62 and LC3 decreased in HeLa cells expressing NSsW61Y, revealing the involvement of individual viral proteins on autophagy. Subsequent experiments confirmed that NSsW61Y perturbs autophagy flux, as evidenced by reduced levels of LC3B and p62 upon treatment with chloroquine, an inhibitor of autophagosome–lysosome fusion. LysoTracker staining demonstrated a decrease in lysosomes in cells expressing the NS mutant compared to those expressing wild-type NS. We further explored the mTOR-associated regulatory pathway, a key regulator affected by NS mutant expression. The observed inhibition of replication could be linked to conformational changes in the NSs, impairing their binding to NP and altering mTOR regulation, a crucial upstream signaling component in autophagy. These findings illuminate the intricate interplay between NSsW61Y and the suppression of host autophagy machinery, which is crucial for the generation of autophagosomes to facilitate viral replication. Full article

Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonosis caused by SFTS virus (SFTSV). In addition to tick bites, animal-to-human transmission of SFTSV has been reported, but little is known about feline SFTSV infection. In this study, we analyzed data on 187 cats with suspected SFTS to identify biomarkers for SFTS diagnosis and clinical outcome. Body weight, red and white blood cell and platelet counts, and serum aspartate aminotransferase and total bilirubin levels were useful for SFTS diagnosis, whereas alanine aminotransferase, aspartate aminotransferase and serum SFTSV RNA levels were associated with clinical outcome. We developed a scoring model to predict SFTSV infection. In addition, we performed a phylogenetic analysis to reveal the relationship between disease severity and viral strain. This study provides comprehensive information on feline SFTS and could contribute to the protection of cat owners, community members, and veterinarians from the risk of cat-transmitted SFTSV infection. Full article

Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes pathogen transmission; however, host cells continuously develop strategies to combat pathogen infection and transmission. Moreover, it is still unknown how host cells develop their defense strategies against tick-borne viruses during tick sucking. Here, we found that the tick saliva peptide HIDfsin2 enhanced the antiviral innate immunity of mouse macrophages by activating the Toll-like receptor 4 (TLR4) signaling pathway, thereby restricting tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) replication. HIDfsin2 was identified to interact with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles, effectively enhancing the activation of the nuclear factor kappa-B (NF-κB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4. Expectedly, TLR4 knockout completely eliminated the promotion effect of HIDfsin2 on NF-κB and type I interferon activation. Moreover, HIDfsin2 enhanced SFTSV replication in TLR4-knockout mouse macrophages, which is consistent with our recent report that HIDfsin2 hijacked p38 mitogen-activated protein kinase (MAPK) to promote the replication of tick-borne SFTSV in A549 and Huh7 cells (human cell lines) with low expression of TLR4. Together, these results provide new insights into the innate immune mechanism of host cells following tick bites. Our study also shows a rare molecular event relating to the mutual antagonism between tick-borne SFTSV and host cells mediated by the tick saliva peptide HIDfsin2 at the tick–host–virus interface. Full article

Background: This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis in the early clinical course. Method: A retrospective study was conducted with confirmed SFTS patients at Jeju National University Hospital (2016–2022). Patients were categorized into non-fatal and fatal groups. Results: This study included 49 patients with confirmed SFTS (non-fatal group, n = 42; fatal group, n = 7). A significant negative correlation (−0.783) was observed between the log SFTS viral load and Ct values (p < 0.001). This negative correlation was notably stronger in the fatal group (correlation coefficient −0.940) than in the non-fatal group (correlation coefficient −0.345). Conclusion: In this study, we established a correlation between SFTS viral load and Ct values for estimating the initial viral load and early predicting prognosis. These results are expected to offer valuable insights for SFTS patient treatment and prognosis prediction. Full article

Haemaphysalis longicornis, a three-host tick with a wide host range, is widely distributed in different countries and regions. It stands out among ticks due to its unique feature of having both parthenogenetic and bisexual populations. Despite their morphological resemblance, the characteristics of the parthenogenetic population have been overlooked. In this comprehensive study, we systematically compared the similarities and differences between these two populations. Our investigation revealed that the parthenogenetic H. longicornis, widely distributed in China, was found in ten provinces, surpassing the previously reported distribution. Notably, individuals from the parthenogenetic population exhibited a prolonged blood-feeding duration during the larval and nymph stages compared to their bisexual counterparts. Additionally, the life cycle of the parthenogenetic population was observed to be longer. A flow cytometry analysis indicated a DNA content ratio of approximately 2:3 between the bisexual and parthenogenetic populations. A phylogenetic analysis using whole mitochondrial genome sequences resulted in the separation of the phylogenetic tree into two distinct branches. A molecular analysis unveiled a consistent single T-base deletion at nucleotide 8497 in the parthenogenetic population compared to the bisexual population. Both populations displayed high viral infection capability and significant resistance to ivermectin. Intriguingly, despite these differences, the parthenogenetic population exhibited a similar life cycle to the bisexual population, retaining the ability to transmit pathogens such as Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland Virus (HRTV). These findings contribute to a deeper understanding of the distinct characteristics and similarities between different populations of H. longicornis, laying the foundation for future research in this field. Full article

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks. Full article

With the ongoing global warming-induced climate change, there has been a surge in vector-borne diseases, particularly tick-borne diseases (TBDs). As the population of companion animals grows, there is growing concern from a One Health perspective about the potential for these animals to spread TBDs. In this study, ticks were collected from companion animals and the surrounding environment in Daejeon Metropolitan City, Korea, using flagging and dragging, and CO₂ trap methods. These ticks were then subjected to conventional (nested) PCR for severe fever with thrombocytopenia syndrome virus (SFTSV), Anaplasma spp., Ehrlichia spp., and Borrelia spp. We identified a total of 29,176 ticks, consisting of three genera and four species: H. longicornis, H. flava, I. nipponensis, and A. testudinarium. Notably, H. longicornis was the predominant species. The presence of A. testudinarium suggested that the species traditionally found in southern regions are migrating northward, likely as a result of climate change. Our PCR results confirmed the presence of all four pathogens in both companion animals and the surrounding environment, underscoring the potential for the indirect transmission of tick-borne pathogens to humans through companion animals. These findings emphasize the importance of the ongoing surveillance of companion animals in the management and control of TBDs. Full article